A Phase III Trial of Lorenzo's Oil in Adrenomyeloneuropathy

洛伦佐油治疗肾上腺脊髓神经病的 III 期试验

• 批准号: 7497531
• 负责人: Gerald V. Raymond
• 金额: $ 107.39万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-18 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497531
• 关键词: 3-Dimensional; Admission activity; Adolescent; Adrenoleukodystrophy; Adrenomyeloneuropathy; Adult; Affect; Biochemical; Brain; Cerebrum; Cervical spinal cord structure; Childhood; Clinical; Clinical Assessment Tool; Clinical Research; Communities; Demyelinations; Depth; Disabled Persons; Disease Progression; Distal; Endocrine; Enrollment; Equilibrium; Esthesia; Evaluation; Exhibits; Imagery; Imaging Techniques; Inflammatory; Institutes; Institution; Intervention; Laboratories; Lorenzo' s oil; Magnetic Resonance Imaging; Male Adolescents; Masks; Measurement; Measures; Medical; Modification; Motion; Multiple Sclerosis; Mutation Analysis; Nervous System Part; Nervous system structure; Neurologic; Nutritional status; Oral Administration; Outcome; Pathogenesis; Pathology; Patients; Phase III Clinical Trials; Phenotype; Placebo Control; Placebos; Plasma; Preventive; Process; Rate; Research Personnel; Score; Sensorimotor functions; Severities; Speed; Spinal Cord Diseases; Spinal Cord Part; Spinal Cord Tract; Standards of Weights and Measures; Structure; Surrogate Markers; Syndrome; Techniques; Testing; Therapeutic Intervention; Therapy Clinical Trials; Tissues; Upper arm; Validation; Very Long Chain Fatty Acid; Week; Woman; axonopathy; boys; cohort; day; design; disability; dorsal column; handicapping condition; innovation; insight; kinematics; men; muscle strength; neuroimaging; novel; placebo controlled study; programs; reconstruction; tool; trierucate; vibration

DESCRIPTION (provided by applicant): The investigators propose to bring to completion a double-masked placebo controlled study of glyceryl trioleate-glyceryl trierucate (Lorenzo's Oil or LO) therapy in adrenomyeloneuropathy (AMN), the adult form of X-linked adrenoleukodystrophy (X-ALD). AMN is a slowly progressive distal axonopathy that involves the long tracts of the spinal cord and differs from the rapidly progressive inflammatory cerebral forms that most commonly affect boys and adolescents. All forms of X-ALD are associated with the abnormal accumulation of very long chain fatty acids (VLCFA) in plasma and tissues. The oral administration of LO normalizes plasma VLCFA levels within four weeks. While previous therapeutic trials of LO therapy in patients with the cerebral forms of X-ALD has been disappointing, recent studies suggest that it is beneficial in two types of X-ALD: 1) as a preventive of neurological involvement in asymptomatic boys; and 2) in AMN, where it appears to slow the rate of progression. None of the previous studies have been controlled, and the investigators are now conducting the first placebo-controlled trial. The four-year study will include 120 men with AMN who do not have evidence of cerebral involvement, and 120 women who are heterozygous for X-ALD and have an AMN-like syndrome. The study is being conducted at the Kennedy Krieger Institute and the General Clinical Research Center at the Johns Hopkins Medical Institutions. The study was initiated in March 2005 and is coordinated by Westat Inc. Eighty patients have been enrolled, and enrollment will be completed in March 2008. The rate of progression will be compared in the LO and placebo groups using the Kurtzke EDSS score as the primary outcome and a variety of secondary outcomes. A novel part of the study is the utilization and validation of newly developed markers, namely magnetization transfer MRI of the cervical spinal cord and quantitative tests of sensation strength and balance in the motion analysis laboratory. These markers test the structure and function of the parts of the nervous system that are most severely involved in AMN. The studies suggest that they will permit more sensitive and rapid assessment of the rate of progression than can be achieved with current techniques. This would accelerate the evaluation of therapeutic interventions in AMN. These techniques may also be applicable to the study of other spinal cord disorders.

描述（由申请人提供）：研究人员提议完成一项双盲安慰剂对照研究，研究三油酸甘油酯-三芥酸甘油酯（洛伦佐油或 LO）治疗肾上腺脊髓神经病（AMN），成人形式的 X 连锁肾上腺脑白质营养不良（X -ALD）。 AMN 是一种缓慢进展的远端轴突病，累及脊髓长束，与最常见影响男孩和青少年的快速进展的炎症性脑病不同。所有形式的 X-ALD 都与血浆和组织中极长链脂肪酸 (VLCFA) 的异常积累有关。口服 LO 在 4 周内使血浆 VLCFA 水平恢复正常。虽然之前针对脑部 X-ALD 患者进行的 LO 疗法的治疗试验令人失望，但最近的研究表明，LO 疗法对两种类型的 X-ALD 有益：1）作为无症状男孩神经系统受累的预防措施； 2) 在 AMN 中，它似乎可以减缓进展速度。之前的研究都没有进行对照，研究人员现在正在进行第一个安慰剂对照试验。 这项为期四年的研究将包括 120 名患有 AMN 且没有脑部受累证据的男性，以及 120 名 X-ALD 杂合子且患有 AMN 样综合征的女性。该研究正在肯尼迪克里格研究所和约翰霍普金斯医疗机构的普通临床研究中心进行。该研究于 2005 年 3 月启动，由 Westat Inc. 协调。已入组 80 名患者，入组将于 2008 年 3 月完成。将使用 Kurtzke EDSS 评分作为主要指标来比较 LO 组和安慰剂组的进展率结果和各种次要结果。该研究的一个新颖部分是新开发的标记物的利用和验证，即颈脊髓的磁化转移 MRI 以及运动分析实验室中感觉强度和平衡的定量测试。这些标记物测试与 AMN 关系最严重的神经系统部分的结构和功能。研究表明，与现有技术相比，它们可以更灵敏、更快速地评估进展速度。这将加速 AMN 治疗干预的评估。这些技术也可能适用于其他脊髓疾病的研究。